Mazdutide is a synthetic dual agonist of the GLP-1 and glucagon receptors, originally licensed from Eli Lilly to Innovent Biologics for development in the Chinese market. Its design is based on oxyntomodulin (OXM), a natural gut hormone that activates both GLP-1R and glucagon receptors. The dual mechanism combines the satiety and glucose-control effects of GLP-1 agonism with the energy-expenditure-increasing effects of glucagon agonism — similar in concept to retatrutide but without the GIP arm. Mazdutide is currently in Phase 3 clinical development across China for obesity and type 2 diabetes, with Phase 3 data showing competitive weight-loss effects.
Mazdutide is a long-acting peptide agonist of two structurally related class B G-protein-coupled receptors: the GLP-1 receptor (GLP-1R) and the glucagon receptor (GCGR). The molecular design is based on oxyntomodulin (OXM), a 37-amino-acid post-translational cleavage product of the proglucagon gene that natively activates both receptors. Mazdutide preserves the dual agonism while extending the plasma half-life through albumin-binding fatty-acid conjugation similar to the strategies used for semaglutide and tirzepatide.
The pharmacologic rationale is to combine the established weight-loss mechanism of GLP-1R agonism (satiety, gastric emptying, glucose-dependent insulin secretion) with the energy-expenditure-increasing effect of GCGR agonism (hepatic glycogenolysis, lipolysis, increased resting metabolic rate). The combination is intended to produce greater weight loss than GLP-1 monotherapy by simultaneously decreasing energy intake and increasing energy expenditure.
Compared with retatrutide, mazdutide lacks the GIP arm — this is the principal pharmacologic difference. The relative weight-loss magnitudes of the two compounds remain an active comparative question in published clinical research.
Mazdutide is in active Phase 3 clinical development in China by Innovent Biologics under multiple programmes covering obesity (GLORY-1) and type 2 diabetes (GLORY-DM). Phase 3 readouts in 2023-2024 documented mean weight reductions of approximately 12-14% at the higher dose cohorts over 48-week protocols — competitive with semaglutide but below the magnitudes reported for tirzepatide and retatrutide.
The compound is approved in China and represents the first dual GLP-1/glucagon agonist to reach pivotal approval. Western market development is anticipated to follow.
Mazdutide is the most clinically-advanced compound in the broader "oxyntomodulin analogue" research class — a category that has been the subject of pharmacologic interest for over a decade, with multiple compounds (cotadutide, etc.) explored across various companies.
The OXM-analogue research thesis predates the contemporary triple-agonist programmes (retatrutide) and represents an alternative pharmacologic strategy: rather than progressively adding receptor arms (GLP-1 → +GIP → +glucagon), the OXM class started from the dual GLP-1 + glucagon design and has remained at that architecture.